Rabies virus (RABV) infection leads to a fatal neurological outcome in humans and animals and is associated with major alterations in cellular gene expression. In this study, we describe the effects of RABV infection on the mRNA expression levels of two genes encoding the Ca2+ binding proteins (Ca-BPs) Calbindin D-28K (Calb1) and Calretinin (Calb2) in the brains of BALB/c mice. Sixty, 4-week-old mice were divided into two test and one control group. Mice were inoculated intra-muscularly with either a street rabies virus (SRV) or Challenge virus standard (CVS-11) strain and sacrificed at 3-day intervals up to day 18 post infection. Direct fluorescent antibody test (DFAT) verified RABV antigen in the brain tissues and real time quantitative PCR (RT-PCR) was used to assess the gene expressions. Infection with both RABV strains resulted in relatively significant (p<0.05) increases in Calb1 and Calb2 expression in the test animals, when compared with the controls at various time points in the study. Correlation analysis indicated very weak insignificant (p>0.05) negative and positive relationships respectively between Calb1 expression (r = -0.04) and Calb2 expression (r = 0.08) with viral load (CVS-11 strain). Insignificant (p>0.05) relationships were also obtained between Calb1 expression (r= -0.28) and Calb2 expression (r = 0.06) with viral load for the SRV strain. The observed alterations in Calb1 and Calb2 expression in this study indicate possible impairments in neuronal Ca2+ buffering and Ca2+ homeostasis as a result of RABV infection and consequently, an implication of Calbindin-D28K and Calretinin in the neuro-pathogenesis of rabies.