Extracellular signalling by purine nucleotides exerts a wide range of biological effects including platelet aggregation, exocrine and endocrine secretion and nociceptive transduction. Yet, some subtypes of ionotropic purinergic receptors have been shown to be predominantly localised in the subpopulation of small nociceptive sensory neurons in dorsal root ganglia (DRG). The aim of this study was to investigate the effects of clopidogrel, the potent antithrombotic agent with high P2Y12 receptor antagonist action on intracellular calcium signalling ([Ca2+]i) in isolated rat sensory neurons. DRG neurons were loaded with 5 μmol Fura-2 AM and Ca2+ responses were assessed by using the fluorescent ratiometry (excitation at 340 and 380 nm, and emission at 510 nm). All data were analyzed by using an unpaired t test, with a 2-tailed P level of <0.05 defining statistical significance. Clopidogrel caused a dose-dependent increase in the [Ca2+]i. The mean 340/380 nm ratio was 0.75±0.02 (baseline, n=6), 0.89±0.01 (10 nM clopidogrel, P<0.01, n=6); 0.85±0.03 (baseline, n=11), 1.10±0.01 (100 nM clopidogrel, P<0.01, n=11); and 0.76±0.02 (baseline, n=32), 1.08±0.02 (1 µM clopidogrel, P<0.001, n=32), respectively. These results indicate that antagonism of the ADP receptors P2Y12 by clopidogrel cause a dose dependent increase in [Ca2+]i indicating involvement of P2Y12 receptor subtype specific purinergic signalling in these sensory neurons which might have importance in nociceptive and neuropathic pain.