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Objective To study the effects of simvastatin on the hypertrophy of cultured rat cardiac myocytes induced by serum and the role of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the signal pathway. Methods Cultured neonatal Sprague-Dawley (SD) rat cardiac myocytes were treated with 15% fetal bovine serum, or without serum, or different consentrations of simvastatin. Image analysis system was used to measure the cardiac myocytes surface area. Protein synthesis of myocytes was measured via [3H]-leucine incorporation method. The expression level of atrial natriuretic peptide (ANP) mRNA in myocytes was determined with reverse transcription polymerase chain reaction (RT-PCR). The mRNA and protein expression levels of PTEN in cardiac myocytes were investigated with RT-PCR and Western blot respectively. Results At 24 hours, cardiac myocytes surface area was significantly higher in 15% serum group (1611.16±160.75 μm2) than in serum-free group (538.04±l18.60 μm2, P