We investigated the protective effect of Erythropoietin (EPO) analogue rHuEPO on renal injury induced by acute exhaustive exercise in the rat. Rats were randomly allocated to one of 3 groups: normal control (C), exhaustive exercise test (ET) and EPO pre-treatment (rHuEPO 2 000 U/kg) plus ET (EPO + ET). Compared with controls, animals in the ET group had increased serum urea nitrogen, serum creatinine, urine protein, and renal tissue malondialdehyde (MDA) and decreased renal tissue nitric oxide (NO), nitric oxide synthase (NOS) and superoxide dismutase (SOD) activities. There was severe damage in renal tubular epithelial cells with a lot of cell apoptosis, and TUNEL assay revealed a remarkably high apoptotic index (p andlt; 0.01). Changes in renal function and kidney tissue were much less in the EPO + ET group (p andlt; 0.05) and the apoptotic index was much lower than in the ET group (18.45 +/- 0.32 vs. 27.55 +/- 0.49, p andlt; 0.05). EPO pretreatment thus significantly prevented renal cell apoptosis, and counteracted high MDA and low NO and NOS renal contents induced by exhaustive exercise. The data point to a potential value of EPO in preventing the acute renal injury after exhaustive exercise.