Abstract: AIM: To investigate the effects of tumor necrosis factor α (TNF-α) on the proliferation of cardiac fibroblast (CF) and the underlying mechanism. METHODS: CFs of neonatal Sprague Dawley rats were isolated by enzymatic dissociation. CF proliferation was measured by thiazolyl blue (MTT) assay and expression of cyclinD1 was detected by RT-PCR and Western blotting. RESULTS: MTT colorimetry showed that the A490 values were 0.417±0.011, 0.622±0.015 and 0.602±0.013, respectively in the 5 μg/L, 10 μg/L and 20 μg/L TNF-α groups, all significantly higher than that in the control group (0.235±0.013, all P<0.05). After stimulation of 5 μg/L and 10 μg/L TNF-α for 36 h, cyclinD1 was upregulated both in mRNA (0.706±0.113, 1.698 ± 0.135) and protein (1.270±0.168, 2.749±0.170) levels compared with those in control group (0.192±0.039 and 0.658±0.101) (all P<0.01). CONCLUSION: Tumor necrosis factor-α promotes CF proliferation through upregulation of cyclinD1. Our findings may provide evidence of using TNF-α signal pathway inhibitor for anti-fibrosis.