AIM To evaluate the antifibrotic effect ofdifferent doses of recombinant human Gamma-Interferon (IFN-γ) intwo rat models of hepaticfibrosis, and to observe its effect on moderatechronic hepatitis B virus fibrosis.METNODS Hepatic fibrosis was successfullyinduced in 150 and 196 rats by subcutaneousinjection of carbon tetrachloride (CCl4) andintraperitoneal injection of dimethylnitrosamine(DMN), respectively. Each of the two modeldose IFN-γ group (15 MU/kg per day, i.m. for 8group (1.67 MU/kg daily, i.m. for 8 weeks).Another group of 10 rats without any treatmentwas used as normal controls. At the end of theexperiment, semi-quantitative histopathologicalscores of inflammation and fibrosis, liver (αsmooth muscle actin (α-SMA) expression level,liver hydroxyl proline content and serumhyaluronic acid levels were compared. And 47medium chronic hepatitis B viral fibrosispatients were studied. They were given IFN-γtreatment, 100MU/day i.m. for the first threemonths and 100MU qod i.m. for the next sixmonths. Semi-quantitative pathological scoresof inflammation and fibrosis and serum hepaticfibrosis indices were compared within the 9months.RESULTS In animal experiment, thepathological fibrosis scores and liver hydroxylproline content were found to be significantlylower in rats treated with different doses of IFN-γ as compared with rats in fibrotic model groupinduced by either CCI4 or DMN, in a dose-dependent manner. For CCI4-induced model,pathological fibrosis scores in high, medium andIow doses IFN-γ groups were 5.10 ± 2.88, 7.70 ±3.53 and 8.00 ± 3.30, respectively, but the scorewas 14.60 ± 7.82 in fibrotic model group.Hydroxyl proline contents were 2.83 ± 1.18, 3.59± 1.22 and 4.80 ± 1.62, in the three IFN-γgroups, and 10.01 ± 3.23 in fibrotic model group.The difference was statistically significant(P＜0.01). Similar results were found in DMN-induced model. Pathological fibrosis scoreswere 6.30±0.48, 8.10 ±2.72 and 8.30 ±2.58, inhigh, medium and Iow doses IFN-γ groups, and12.60 ± 3.57 in fibrotic model group. Hydroxylproline contents were 2.72 ± 0.58, 3.14 ± 0.71and 3.62 ± 1.02, in the three IFN-γ groups, and12.79 ± 1.54 in fibrotic model group. Thedifference was statistically significant(P＜0.01). Serum hepatic fibrosis indicesdecreased significantly in the 47 patients afterIFN-γ treatment (HA: 433.38 ± 373.00 vs 281.57± 220.48; LN: 161.22± 41.02 vs 146.35 ± 44.67;PCⅢ: 192.59 ± 89.95 vs 156.98 ± 49.22; C-Ⅳ:156.30 ± 44.01 vs 139.14 ± 34.47) and thedifferences between the four indices weresignificant (P＜0.05). Thirty-three patientsCONCLUSION All the three doses of IFN-γ areeffective in treating rat liver fibrosis induced byeither CCl4 or DMN, the higher the dose, thebetter the effect. And IFN-γ is effective forpatients with moderate chronic hepatitis B viralfibrosis.