Genetic variation has been observed for susceptibility/ resistance to several infectious diseases in cattle. Superiority of Bos indicus breeds over Bos taurus breeds for disease resistance trait has been reported by several workers. Therefore the objective of this study was to analyze expression profiles of genes with well characterized roles in immune response using qRT-PCR in indigenous Tharparkar and crossbred Vrindavani cattle and to assess whether significant variation exists in gene expression between two breeds of cattle. Eighteen genes in two groups with GAPDH as reference were investigated for mRNA expression. Ten out of eighteen genes under investigation namely TLR2, NFKB1, TNF, IFNG, IL2, CXCR3, PRKCB1, RPS6KB2, STK17B and EEF1 genes revealed significantly higher expression in indigenous Tharparkar cattle as compared to Vrindavani cattle. Whereas, no significant difference was observed for expression of IL16, CCL1, EEF1G, CD84, MCL1, NFATC4 and IER-5 genes between Tharparkar and Vrindavani cattle. Expression of CD-81 gene was significantly lower in Tharparkar as compared to Vrindavani. Investigation revealed higher basal expression in majority of innate response genes under study in Tharparkar as compared to Vrindavani indicating a superior level of basal immune competence in Tharparkar. This can be a possible reason for differences in susceptibility/resistance in indigenous and crossbreds to various invading bacterial and viral pathogens.