Objective To observe the effects of rosiglitazone (RGZ) on the proliferation of HELF cells( human embryonic lung fibroblast) and p38 / MAPK signaling. Methods HELF cells were cultured in DMEM medium. The cells were divided into a control group, TGF-β1 group, low dose RGz (LD-RGZ) group, and high dose RGZ (HD-RGZ) group. CCK-8 was used to detect cell proliferation, and the cell cycle was detected by flow cytometry. Western blot was used to detect protein expression. Results At 24, 48, and 72 h, the OD₄₅₀ values in the HD-RGZ group were significantly lower than those in the LD-RGZ group (P< 0. 05), and those in the LD-RGZ group were significantly lower than the values in the TGF-β1 group (P< 0. 05). The proportion of G1 phase cells in the control, TGF-β, LD-RGZ, and HD-RGZ groups was (91. 23 ± 6. 32)%, ( 70. 35 ± 4. 14)%, ( 76. 12 ± 4. 38)%, and ( 82. 35 ± 5. 16)%, respectively. There was a significant difference among the groups ( P< 0. 05 ). The percentage of G1 phase cells in the HD-RGZ group was significantly higher than that in the LD-RGZ group (P< 0. 05), and the proportion in the LD-RGZ group was significantly higher than that in the TGF-β1 group (P< 0. 05). The protein expression of Col I, Col III, and phospho-p38 / MAPK in the HD-RGZ group was significantly lower than that in the LD-RGZ group (P< 0. 01), and the levels in the LD-RGZ group were significantly lower than those in the TGF-β1 group ( P< 0. 01). Conclusions RGZ can inhibit the p38 / MAPK pathway to impair the proliferation and collagen synthesis of pulmonary fibroblasts.