Although the efficacy of MSCs on the liver fibrosis is investigated, it is not exactly clear whether released mols. by MSCs are sufficient to mediate the anti-fibrotic effects or not.In this study, the possible hepatoprotective effects of human umbilical cord MSCs derived conditioned medium (UC-CM) was investigated. 30 male rats were divided into 3 groups (n = 10): C: control; F: fibrosis were i.p. injected with CCl4 (1 mL/kg, i.p); F/UC-CM: fibrosis rats that received UC-CM (100μg/kg, i.v).At the end of the 12th week, serum and liver samples were collected to analyze biochem., mol., and histopathol. parameters.In comparison with CCl4 intoxicated animals, the results showed a significant amelioration of weight loss, histol. changes as well as attenuation of serum activity of ALT, AST, and ALP in F/UC-CM.The liver hydroxyproline content was significantly reduced by UC-CM treatment.Accordingly, improvement in oxidative parameters such as MDA, TAC, and TOS was also observed in the F/UC-CM group.UC-CM administration down-regulated gene expression of TGF-β1, TNF-α, TβRII, MMP-2, and MMP-9 as well as the protein level in TGF-β1 and TNF-α.Immunohistochem. anal. showed a notable lower hepatic α-SMA expression in the F/UC-CM group.In conclusion, these findings revealed that the remarkable hepatoprotective property of UC-CM could lend support to its anti-inflammatory and antioxidative and anti-fibrotic effects.