<jats:title>Abstract</jats:title><jats:sec><jats:title>Aim</jats:title><jats:p>To evaluate the influence of the addition of microparticulate (micro) and nanoparticulate (nano) zirconium oxide (ZrO<jats:sub>2</jats:sub>) and niobium pentoxide (Nb<jats:sub>2</jats:sub>O<jats:sub>5</jats:sub>) to a calcium silicate‐based cement (<jats:styled-content style="fixed-case">CS</jats:styled-content>) on the subcutaneous healing process in rats compared with <jats:styled-content style="fixed-case">MTA</jats:styled-content> Angelus™.</jats:p></jats:sec><jats:sec><jats:title>Methodology</jats:title><jats:p>In each rat, two polyethylene tubes filled with the following materials: (i) <jats:styled-content style="fixed-case">MTA</jats:styled-content>; (ii) <jats:styled-content style="fixed-case">CS</jats:styled-content> + ZrO<jats:sub>2</jats:sub>micro; (iii) <jats:styled-content style="fixed-case">CS</jats:styled-content> + ZrO<jats:sub>2</jats:sub>nano; (iv) <jats:styled-content style="fixed-case">CS</jats:styled-content> + Nb<jats:sub>2</jats:sub>O<jats:sub>5</jats:sub>micro or (v) <jats:styled-content style="fixed-case">CS</jats:styled-content> + Nb<jats:sub>2</jats:sub>O<jats:sub>5</jats:sub>nano were implanted subcutaneously; empty polyethylene tubes were used in the Control group. After 7, 15, 30 and 60 days, the specimens (<jats:italic>n</jats:italic> = 5 per group in each period) were fixed and embedded in paraffin. Masson's trichrome sections were used to obtain the volume density of the inflammatory cells (Vv<jats:styled-content style="fixed-case">IC</jats:styled-content>) and fibroblasts (VvFb). The sections were also stained with Picrosirius‐red to calculate the birefringent collagen content. Fibroblast growth factor‐1 (<jats:styled-content style="fixed-case">FGF</jats:styled-content>‐1) was detected by immunohistochemistry, and the number of immunolabelled cells was obtained. The data were subjected to two‐way <jats:sc>anova</jats:sc> followed by Tukey's test (<jats:italic>P</jats:italic> ≤ 0.05).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>At all periods, the Vv<jats:styled-content style="fixed-case">IC</jats:styled-content> was significantly lower (<jats:italic>P</jats:italic> < 0.001) in all the <jats:styled-content style="fixed-case">CS</jats:styled-content> and Control groups than in the <jats:styled-content style="fixed-case">MTA</jats:styled-content> group. At all periods, the VvFb was reduced significantly (<jats:italic>P</jats:italic> = 0.023) in the <jats:styled-content style="fixed-case">MTA</jats:styled-content> group in comparison with the other groups. In addition, the number of immunolabelled cells in the capsules of the <jats:styled-content style="fixed-case">CS</jats:styled-content> groups was significantly higher (<jats:italic>P</jats:italic> < 0.001) than in the <jats:styled-content style="fixed-case">MTA</jats:styled-content> group at all time‐points.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The experimental materials (<jats:styled-content style="fixed-case">CS</jats:styled-content> + ZrO<jats:sub>2</jats:sub> and <jats:styled-content style="fixed-case">CS</jats:styled-content> + Nb<jats:sub>2</jats:sub>O<jats:sub>5</jats:sub>) induced fibroblast proliferation and accelerated the regression of the inflammatory reaction. However, the addition of nanoparticulate radiopacifiers did not improve the biological properties of a calcium silicate‐based cement when compared to microparticulate agents.</jats:p></jats:sec>