The aim of the present study was to explain whether serum autotaxin activity might bea target for regulation of liver fibrosis and to evaluate the hepato-protective and antifibroticeffects of histidine in thioacetamide induced liver fibrosis in rats. The studywas carried out on 100 albino rats, classified into 5 groups each of 20 rats: group І(control group), group ІІ: rats were given histidine intra-peritoneally, group ІІІ: ratswere injected intra-peritoneally with thioacetamide, group IV: rats were injected withL-histidine together with thioacetamide, group V: rats were injected with TAA for onemonth then treated with intra-peritoneal injection of L-histidine for another month. Atthe end of experiment, blood and liver were collected for determination of some liverenzymes, plasma total antioxidant capacity, serum autotaxin activity and liver tissuehydroxyproline. Thioacetamide treatment caused significant increases in liverenzymes, autotaxin activities and liver hydroxyproline, but with a significant decreasein plasma total antioxidant capacity. Upon treatment with histidine significantdecreases in liver enzymes, autotaxin activities and liver hydroxyproline wereobserved with a significant increase in plasma total antioxidant capacity in group IVand significant decrease in group V. Conclusion: histidine as an antioxidant has aprotective effect on thioacetamide-induced liver fibrosis , its beneficial effects in ratsmight be not only by inhibition of collagen synthesis and increasing total antioxidantcapacity, but also by inhibition of autotaxin activities, thus reducing its capacity toproduce lysophosphatidic acid which has a role in liver fibrosis.