•GABAC ρ3 expression decreases in the cortex, striatum and hippocampus of HD tg mouse brain.•Loss of GABAc ρ3 receptor immunoreactivity may account for diminished inhibitory input and neurodegeneration in HD.•Activation of GABARs and inhibition of glutamatergic pathway might protect neuronal loss in HD. In the present study, we describe the distribution of GABAC ρ3 receptor immunoreactivity in the cortex, striatum and hippocampus of wild type (wt) and 11 weeks old HD transgenic (tg) R6/2 mouse brain. In the brain of wt mice, GABAC ρ3 immunoreactivity is well expressed in neuronal cells, nerve fibers and axonal processes. In comparison to wt, GABAC ρ3 receptor like immunoreactivity decreases significantly in all three brain regions of R6/2 mice. The altered distributional pattern and significant changes in GABAC ρ3 receptor immunoreactivity as seen in the R6/2 mouse brain might be a plausible molecular mechanism for excitotoxicity in HD pathogenesis due to the loss of inhibitory input.