Capsular contracture is a potential adverse effect of breast implants. An inflammatory reaction is most likely the origin of fibrosis around the implant. It is possible that some substances may act to prevent this inflammatory reaction. Thus, our goal was to evaluate the effectiveness of local depot prednisolone phosphate-liposomes (PPL) on fibrous capsule formation around textured silicone breast implants. Shell prostheses (2 mL) were implanted in the right (plus PPL group) and left (plus saline solution, saline group) subcutaneous dorsum of 18 rats. In another 18 rats, the implants were positioned in the left of the back without any drug instillation (control group). In the PPL group, the capsule thickness (microm) and density (%) of collagen were significantly (p<0.0001) lower compared with the control group on days 35 and 90 postsurgery. Furthermore, in the PPL group, a significant reduction in myofibroblast count was observed on day 90 postsurgery (p<0.0001). In conclusion, a single dose of depot liposome-delivered prednisolone was effective at impairing capsule formation around the silicone implant. The results suggest a strong local and weak systemic effect of PPL on the fibrous tissue around silicone implants. To our knowledge, no study has yet assessed the effect of PPL on silicone breast implants.