Abstract: Objective To establish a stable and effective inducible cardiomyocyte-specific Ppara ( gene of peroxisome proliferator - activated receptor α, PPARα ) -deficient mice model, the effects of different tamoxifen administration on PPARα knockout efficiency and cardiac function in these inducible cardiomyocyte-specific Pparadeficient mice. Method Ppara^{fl / fl}, ^myh6-ERT2Cre mice and the littermate control ( Ppara^{fl / fl} ) mice were obtained by mating and backcross between Pparafl / fl mice and ^Myh6-ERT2Cre mice. Group A ( mice were intraperitoneally injected with a single dose of 2 mg tamoxifen) , group B ( mice were intraperitoneally injected with 20 mg / kg· d tamoxifen for 5 days) and group C ( mice were intraperitoneally injected with 40 mg / kg· d tamoxifen for 5 days) . Two weeks after administration of tamoxifen, the cardiac function was monitored by echocardiography, myocardial fibrosis was observed with Masson staining and the PPARα expression was detected by Real-time qPCR and Western blot. Result Compared with the vehicle group, the cardiac function of mice in group A was not affected, as Real-time qPCR showed that the knockdown efficiency of Ppara in the myocardium was insufficient. While, in group B and group C, results of Real-time qPCR and Western blot confirmed the loss of PPARα in cardiomyocytes, and the echocardiography and histology indicated that the cardiac function of mice was normal in group B, but injured in group C. Conclusion These data suggested that intraperitoneal injection of 20 mg / kg tamoxifen for 5 consecutive days on Ppara^{fl / fl}, ^myh6-ERT2Cre mice can induce Ppara knockdown in cardiomyocytes sufficiently, leading to a successful establishment of inducible cardiac-specific Ppara deficient mice model.