Abstract： Chief aim of the present work was to investigate vasonatrinpeptide (VNP) attenuates hypoxia-induced expression of c-fos gene in cardiac fibroblasts from cultured neonatal rats. The cultured cardiac fibroblasts were divided randomly into four groups: Control group, hyoxia group (20～30 mL·L-1), VNP group (10-8～10-6 mol·L-1) and VNP (10-6 mol·L-1)+hypoxia group. The c-Fos expression of cardiac fibroblasts was measured by the means of immunocytochemistry, [Ca2+]i concentration was measured by the means of interactive laser cytometer. The studies performed with these techniques show that hypoxia increased significantly the positive cells and mean grey of cardiac fibroblasts (P<0.05 vs control group), VNP decreased the positive cells (P<0.05 vs control group) and decreased the level of [Ca2+]i in VNP+hypoxia group. These findings indicate that VNP can attenuate hypoxia-induced expression of c-fos gene in cardiac fibroblasts which was associated with the changes of the[Ca2+]i.