Aim To explore the protective effect of lovastatin on endothelial dysfunction induced by homocysteine thiolactone (HTL) and potential mechanism. Methods 90 min after the co-incubation of aorta rings with various agents, both the acetylcholine (Ach) -induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation of aortic rings were examined, and the biochemical parameters including content of malondialdehyde (MDA), level of nitric oxide (NO) and activity of superoxide dismutase (SOD) in vascular tissue were also measured. Results After incubation with HTL for 90 minutes, Ach-induced EDR was significantly decreased, while SNP-induced endothelium-independent relaxation was not affected. HTL also markedly reduced the levels of NO and SOD activity, and increased the content of MDA in rat aorta tissue, compared with normal control group (P<0.05). The lovastatin 10, 20 and 40 μmol/L improved the EDR, the Emax was increased from 39.72%±1.91% to 54.84%±1.89%, 66.25%±1.93%, 80.12%±1.32% respectively; half effective concentration (EC50) was decreased from 230.45±13.42 nmol/L to 145.34±13.19 nmol/L, 126.93±12.91 nmol/L, 109.16±14.20 nmol/L respectively; while the NO level was increased from 0.26±0.04 mmol/g to 0.51±0.05 mmol/g, 0.67±0.03 mmol/g, 0.88±0.04 mmol/g; The lovastatin also decreased the MDA level and maintained SOD activity induced by HTL in rat aorta compared with alone HTL group (P<0.05 or 0.01). However, the incorporating of lovastatin with L-NAME abolished the protective effect of lovastatin on endothelial function damaged by HTL. SOD, the antioxidant NAC and the nitric oxide precursor L-arginine also ameliorated the impaired EDR induced by HTL. Conclusion Lovastatin can protect from endothelial function injury by HTL. The mechanism may be related to protecting release of NO and suppressing the generation of oxygen-free radicals.