The efficacy of opioids in chronic pain treatment is limited because of the development of opioid tolerance. We investigated the role of N-methyl-D-aspartate (NMDA) receptor antagonists (NMDAR Ants) in morphine analgesia and tolerance in rats. To induce the morphine tolerance, experimental rats received morphine (50 mg/kg; subcutaneously) once daily for 3 days. After the last dose of morphine was injected on day 4 and morphine tolerance was evaluated, analgesic effects of ketamine, dizocilpine (MK-801, a non-competitive NMDAR Ant), LY235959 (a competitive NMDAR Ant), cis-2,3-piperidinedicarboxylic acid (PDA, an NMDAR agonist), and morphine were estimated with 30-min-long intervals (0, 30, 60, 90, and 120 min) by the tail-flick and hot-plate algesia tests (n = 6 in each studied group). As was found, ketamine, MK-801, and LY235959 significantly attenuated the development of morphine tolerance (P < 0.05). On the other hand, PDA somewhat increased the development of this tolerance, but the difference was not statistically significant (P > 0.05). Our data indicate that NMDAR Ants attenuate the development of morphine tolerance, significantly affecting the effects of morphine analgesia in rats.