Abstract: AIM: To investigate the effect of peroxisome proliferator-activated receptor-α (PPARα) agonist fenofibrate on the proliferation of rat cardiac fibroblasts (CFs) induced by chymase and its mechanism of action. METHODS: Cultured CFs from neonatal SD rats were isolated by trypsinization and the DNA synthesis and cellular cycle of the CFs were evaluated, respectively, by 3H-TdR incorporation and flow cytometry. mRNA expressions of PPARα and TGF-β1 in the CFs were determined by RT-PCR. RESULTS: Pretreatment with fenofibrate decreased the 3H-TdR incorporation of the CFs in a concentration-dependent manner. The 3H-TdR incorporations pretreated with 50 and 100 μmol/L fenofibrate were significantly lower than those in the chymase group (P<0.05, P<0.01). Cellular cycle analysis showed that pretreatment with 50 and 100 μmol/L fenofibrate markedly increased the cellular percentage in G0/G1 stage and decreased the cellular percentage in S stage and proliferation index compared with those in the chymase group (P<0.05, P<0.01). Pretreatment with fenofibrate increased the PPARα mRNA and decreased the TGF-β1 mRNA in a dose-dependent manner. PPARα mRNA pretreated with 50 and 100 μmol/L fenofibrate was higher than in the chymase group (P<0.05, P<0.01) and the TGF-β1 mRNA was lower than in the chymase group (P<0.01). CONCLUSION: PPARα agonist fenofibrate inhibits the proliferation of rat CFs induced by chymase possibly through the upregulation of PPARα mRNA and the downregulation of TGF-β1 mRNA, suggesting that there may be cross-talk between the PPARα and TGF-β1 signal pathways.