Aim:To study the alteration of major milk components such as milk fat, protein, lactose, solid not fat (SNF) and total solids (TS) and their association with different degree of intra-mammary inflammation (IMI) in Jaffrabadi buffaloes.Materials and Methods:Milk samples (n=1516) were collected from Jaffrabadi buffaloes separately from each quarter. Milk samples were analyzed for milk fat, protein, lactose, SNF and TS percent on the same day using milk analyzer “LACTOSCAN.” Milk samples were checked for IMI by California mastitis test (CMT), and the results were expressed as negative (0), +, ++, and +++ CMT score. The traits of milk components which showed significant difference (p<0.05) between samples from inflamed and non-inflamed quarters were analyzed by receiver operating characteristic (ROC) analysis to see the accuracy and degree of association with IMI.Results:Among several milk components, milk protein and lactose percent showed a significant difference (p<0.05) between milk samples from normal and inflamed quarters. Though, during the early stage of mammary gland inflammation milk protein percent remained significantly high (p<0.05), later with an increase in the degree of severity of inflammation it did not show any difference. Milk samples from normal udder quarters had significantly higher lactose percent than inflamed quarters (p<0.05). Milk lactose percent decreased gradually with an increase in the degree of severity of inflammation. ROC analysis revealed that milk samples having lactose content below the threshold values had significantly higher chances to come from inflamed udder quarters (p<0.05). Though, the value of the area under curve (AUC) indicated that milk lactose was significantly associated with IMI (p<0.05), the accuracy was moderate (AUC=0.71-0.75).Conclusions:The results of the present study indicated that milk lactose percent gradually and significantly reduced during IMI and can be used as a marker for identification of IMI in buffaloes. However, ROC analysis further confirmed that using milk lactose IMI can be identified with moderate accuracy.