Context: The effects of icariin, a chief constituent of ?avonoids from Epimedium brevicornum Maxim (Berberidaceae), on the levels of HIF-1 alpha, HSP-60 and HSP-70 remain unknown. Objective: To explore the effects of icariin on the levels of HSP-60, HIF-1 alpha and HSP-70 neuron-specific enolase (NSE) and cell viability. Materials and methods: PC12 cells were treated with icariin (10(-7), 10(-6) or 10(-5) mol/L) for 3h (1h before oxygen-glucose deprivation (OGD) plus 2h OGD). HSP-60, HIF-1 alpha, HSP-70 and NSE were measured using enzyme-linked immunosorbent assay (ELISA). Cell viability was determined by metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: After 2?h OGD, levels of HIF-1 alpha, HSP-60, HSP-70 and NSE were increased significantly (HIF-1 alpha: 33.3 +/- 1.9 ng/L, HSP-60: 199 +/- 16 ng/L, HSP-70: 195 +/- 17 ng/L, NSE: 1487 +/- 125 ng/L), and cell viability was significantly decreased (0.26 +/- 0.03), while icariin (10(-7), 10(-6), or 10(-5) mol/L) significantly reduced the contents of HIF-1 alpha, HSP-60, HSP-70 and NSE (HIF-1 alpha: 14.1 +/- 1.4, 22.6 +/- 1.8, 15.7 +/- 2.1, HSP-60: 100 +/- 12, 89 +/- 6, 113 +/- 11, HSP-70: 139 +/- 9, 118 +/- 7, 95 +/- 9 and NSE: 1121 +/- 80, 1019 +/- 52, 731 +/- 88), and improved cell viability (0.36 +/- 0.03, 0.38 +/- 0.04, 0.37 +/- 0.03) in OGD-treated PC12 cells. Discussion and conclusion: These results indicate that the protective mechanisms of icariin against OGD-induced injury may be related to down-regulating the expression of HIF-1 alpha, HSP-60 and HSP-70.