This research work was conducted to study the effect of edible oil on serum pro inflammatory cytokines (IL-6 and TNF-α) and anti-inflammatory cytokine (IL-10), Liver histological changes in experimental rabbits and HMGCR and G6PDH gene expression pattern in rabbit liver. Edible oils are generally used in home cooking and industrial food manufacturing worldwide and are the major source of unsaturated fats in human diets. Moreover, as with all food products, there is a probable for potentially toxic contaminants to occur in oils. An experimental study design was conducted eighteen albino rabbits were fed with rabbit food pallets for 21 days, of which 06 were fed normal diet (Group-I), and the other 06 were fed with edible oil at 2 ml/kg + normal feed (Group-II), third group of 06 rabbits were fed edible oil at 5 ml/kg + normal feed (Group-III). Estimation of cytokines levels in serum and the expression levels of HMGCR and G6PDH genes in rabbit liver were determined by using real-time fluorescent quantitative PCR and Western blot. The expressions of HMGCR and G6PDH mRNAs, protein levels and activity in Group-II and group - III were significantly over expressed as compared with those in Group-I. Low levels of SOD and CAT were observed in liver of Group -III rabbits compared with Group-II and Group-I. It was concluded that edible oil showed regulative effect on liver by a potential mechanism of high expression HMGCR and G6PDH genes, protein abundance, activity of HMGCR and G6PDH and low concentrations of SOD and CAT in serum, consequently histopathological alterations are observed in edible oil experimental rabbit liver.