The present study aimed to investigate the biochemical, antioxidant and histopathological factors & consequences which alter the defensive role of 50% hydro-alcoholic Caesalpinia bonducella seed kernel extract (CBSKE) (100 & 200 mg/kg b. wt.) of total Phenolic content on the experimentally induced mastitis by Staphylococcus aureus in the late lactating rats. Thirty lactating rats were randomly divided into five groups (n=6); physiological saline treatment (control) group-I, S. aureus induced (diseased) group-II, S. aureus + CBSKE treated (extract treatments) groups- III & IV and standard antibiotic Ciprofloxacin treated group-V. The concentration of S. aureus was adjusted to 2×107CFU/ML and inoculated into the abdominal fourth right and left (R4 & L4) mammary glands via the teat duct on the 14th day of lactation. After inoculation, simultaneous treatments were started orally. Dosage has been given per 6h time interval. Rats were euthanized at 72h of post treatment in each group. The blood and liver tissue were collected for biochemical, antioxidant and histological evaluation. The CBSKE treated groups exhibited more relevance to the antibiotic treated group more than the S. aureus treated group. Serum total urea, urea nitrogen, creatinine, uric acid, total protein, albumin globulin, AST, ALT, ALP, GGT, amylase and creatinine kinase in level of significance and antioxidant enzymes revealed a significant increase in the lipid peroxidation. Other antioxidants are significantly decreased in the activity levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase, glutathione reductase and reduced glutathione. Further, histological alterations also suggest that the central vein and hepatocytes indicate recovery in treatment groups compared to the diseased group. The phenolic fraction of CBSKE exhibited more potential as an anti-mastitis therapeutics in a rat model.