OBJECTIVE： To study the improvement effects and its mechanism of erythropoietin derivative helix B surface peptide （HBSP） on epirubicin-induced myocardial injury in rats. METHODS： SD rats were randomly divided into control group， model group， erythropoietin （EPO） group and HBSP group， with 10 rats in each group. Except for control group， other groups were given epirubicin 2.5 mg/kg intraperitoneally， once a week， for consecutive 6 weeks to induce myocardial injury model. EPO group and HBSP groups were given rhEPO 5 000 u/kg or HBSP 60 μg/kg intraperitoneally， 3 times a week （one day before medication， first day and third day after medication of epirubicin）， for consecutive 6 weeks. At the beginning of the first administration， the rats were weighed at the 11th week. The cardiac function was measured by echocardiography [left ventricular end-diastolic diameter （LVIDd）， ejection fraction （EF）， fractional shortening （FS） and cardiac output（CO）]. The serum levels of troponin I （cTnI） and amino-terminal B-type natriuretic peptide （NT-proBNP） were determined by ELISA. mRNA expression of PI3K and Akt in myocardial tissue was detected by RT-PCR. The protein expression of p-PI3K and p-Akt in rat myocardium were detected by Western blot. RESULTS： During research period， two rats died in model group， one in EPO group and none in HBSP group. Compared with control group， body weight， the levels of EF， FS and CO were decreased significantly in model group， while the contents of LVIDd and cTnI， NT-proBNP were increased significantly； mRNA expression of PI3K and Akt as well as protein expression of p-PI3K and p-Akt were decreased significantly， above differences were statistical significant （P＜0.05）. Compared with model group， body weight， the levels of EF， FS and CO were increased significantly in EPO group and HBSP group， while the contents of LVIDd and cTnI， NT-proBNP were decreased significantly； mRNA expression of PI3K and Akt as well as protein expression of p-PI3K and p-Akt were increased significantly， above differences were statistical significant （P＜0.05）. Compared with EPO group， the contents of cTnI and NT-proBNP were decreased significantly in HBSP group， with statistical significance （P＜0.05）. CONCLUSIONS： HBSP can improve myocardial injury in rats as much as EPO， and has less toxity. Their mechanism may be related to the activation of PI3K/Akt signaling pathway.