AIM: To investigate the gene expression of proteins handling the calcium homeostasis in diabetic rat heart. METHODS: Diabetes was induced in male Sprague-Dawley rats (180-220)g by administering a single tail-vein injection (40mg/kg ) of alloxan, and the control group was injected with normal saline. At the end of four, six weeks after the induction of diabetes, the animals were killed for assessment of the ventricular gene expression of proteins handling the calcium homeostasis which was measured by reverse transcription-polymerase chain reaction and nomalized to the mRNAs level of actin. RESULTS: At the end of 4 and 6 weeks, the weight of body and the heart in the diabetic group is lower than that in control rats, heart to body weight of diabetic rats is higher than control. No changes in mRNAs level of sarcoplasmic reticulum calcium ATPase, phospholamban, ryanodine receptor type 2, 1,4,5-trisphosphate inositol receptor type 2 were observed 4 weeks after alloxan injection. Expression of phospholamban mRNAs was significantly increased, but ryanodine receptor type 2, 1,4,5-trisphosphate inositol receptor type 2 mRNAs were significantly decreased than that in the age-matched controls. In contrast, expression of mRNAs coding sarcoplasmic reticulum calcium ATPase was not affected 6 weeks after alloxan injection. CONCLUSION: Gene expression of phospholamban is increased while ryanodine receptor type 2, 1,4,5-trisphosphate inositol receptor type 2 are decreased in the diabetic rat heart. [