Acupuncture and acupressure points correlate well with sites on the body that have low transcutaneous electrical resistance (TER). Using lightly sedated, adult Sprague-Dawley rats, we identified an acupoint (i.e. site with low TER) located on the hind limb of the rat and compared the effects of acupressure at this site on the nociceptive threshold to an adjacent, non-acupoint site (i.e. site with high TER). Focal pressure (55.42 +/- 2.2 g) was applied to the site for 10 minutes and the tail flick response (TFR) was determined by draping the distal portion of the tail over a heated wire (75 +/- 5 degrees C). Three trials were performed during each of three randomized conditions (i.e. acupoint, placebo and control) and the trials were averaged. All rats tested (5/5) showed a statistically significant increase in TFR following 10 minutes of acupressure at the acupoint compared to placebo or control trials (p = 0.007). Acupressure at the placebo point resulted in a TFR that was not statistically different from the control. Systemic administration of naloxone completely abolished the tail-flick inhibition induced by acupressure at the acupoint. These data suggest that acupressure elicits an antinociceptive effect in rats that is mediated by the endogenous release of opioids.