The present investigation was conducted on lactating buffaloes from Animal Farm CCS HAU Hisar and also from Hisar city and surrounding areas on some aspects of pathogenesis and therapy of sub-clinical mastitis. Indirect laboratory diagnostic tests like California mastitis test (CMT), somatic cell count (SCC) and milk conductivity test (MCT) were employed to diagnose these cases by which animal wise prevalence rate was found to be 9.62 %(18 out of 187 animals) whereas quarter wise prevalence rate was 2.44 % (18 out of 736 quarters).These rates were quite lower than those reported in literature by workers from same areas It was also found that CMT and SCC were comparatively superior tests for such diagnosis compared to MCT since former two tests were able to diagnose all the 18 cases which were considered positive while by MCT, 4 out of these 18 cases gave negative results. Hematological examination of diseased animals revealed leukocytosis and neutrophilia along with relative lymphopenia/monocytopenia and eosinophilia which was in accordance with the reports in literature. Absolute counts of individual erythrocytes also followed more or less similar pattern except in case of lymphocytes. Assessment of oxidative stress related changes showed a significantly lower level of serum inorganic phosphorus in animals with sub-clinical mastitis along with a significantly higher level of blood/milk malondialdehyde which is an indicator of lipid peroxidation in the body. These changes clearly indicated that oxidative stress is a component of pathogenesis of sub-clinical mastitis. Therapeutic studies conducted on cases of sub-clinical mastitis in buffaloes indicated that a commonly used antibiotic enrofloxacin when combined with an antioxidant (ascorbic acid) as adjunct was highly effective (100.00%) as compared to enrofloxacin alone (83.33%) or a homeopathic drug combination (Phytolacca 200, Bryonia 200, Silicea 200, Aconite 200 and Belladonna 200), efficacy of which was found to be 66.66%. Results of therapeutic trial also revealed that oxidative stress has a considerable role in the pathogenesis of sub-clinical mastitis and ascorbic acid has a potential to be an ideal adjunct to antibiotic therapy of this disease.