Abstract: Aim: To investigate the effect of Aspirin on endothelin-1 induced proliferation of cardiac fibroblasts (CFs). Methods: Isolated and cultured CFs from neonatal Sprague-Dawley rats (SD) were randomly divided into 7 groups: ①control, ②ET-1, ③Aspirin, ④ET-1+ Aspirin 1mmol/L, ⑤ET-1+ Aspirin 2mmol/L, ⑥ET-1+ Aspirin 5mmol/L and ⑦ET-1+ Aspirin1 10mmol/L. CFs were counted by MTT assay. Cell cycle distribution was determined with a flow cytometer (FCM). [3H]-Proline incorporation was evaluated by scintillation counting. Nitric oxide (NO) was measured by colorimetry. Results: 10-7mol/L ET-1 significantly increased the number of CFs and [3H]-Pro incorporation and decreased NO2-/NO3- secretion compared with the control group (P < 0.01). 1-10mmol/L Aspirin inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P < 0.05 vs ET-1). In the ET-1 group, the percentage of cells in the S phase was higher than control, which was inhibited by 10mmol/L Aspirin (P< 0.01 vs ET-1 and control). Conclusion: Aspirin can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.