Bleomycin is a chemotherapeutic agent with side effects especially skin. Simvastatin is a cholesterol lowering drug with immunomodulatory, anti-inflammatory and antifibrotic effects. Pioglitazone is a peroxisome proliferator-activated receptor- γ anti-diabetic with antiproliferative, antioxidant and anti-inflammatory actions. The aim of this study was to investigate the anti-inflammatory and antifibrotic efficiency of simvastatin and pioglitazone each alone and in combinations against bleomycin - induced changes in mice thin skin using histological, immunohistochemical techniques. The duration of the study was 3 weeks by which 75 mice (8 weeks old) were used and divided into 7 groups. Control group, group 1 that received 100 µl bleomycin subcutaneous, group 2 which received simvastatin (5 mg/kg /day) orally, group 3 that received pioglitazone (10 mg/kg/day) orally, group 4 which received simvastatin (5 mg/kg /day) orally 1 hr. before the subcutaneous dose of bleomycin, group 5 that received pioglitazone (10 mg/kg/day) orally 1 hr. before bleomycin and group 6 received simvastatin (5 mg/kg /day) and pioglitazone (10 mg/kg/day) orally 1 hr. before bleomycin. In group 2; dermal thickening, subcutaneous fat atrophy, degenerated hair follicles, thickened cutaneous vessels observed beside significant increase in caspase-3 reaction. Reversal of the previous findings markedly observed in group 6 than in group 4, 5. We conclude that, the concurrent administration of pioglitazone and simvastatin enhanced their beneficial effects in the reversal of bleomycin-induced changes in mice thin skin.