AIM: To investigate the effects of nocistatin and nocistatin (10-17) on nociceptin in antagonizing endomorphin-1 or endomorphin-2 analgesia in mice. METHODS: Nocistatin and nocistatin (10-17) were synthesized by solid-phase peptide synthesis method. The mouse tail-flick test was used to assess the pain threshold of the mice and observe the effects of nocistatin and nocistatin (10-17). RESULTS: Nociceptin was shown to antagonize endomorphin-1 and endomorphin-2 analgesia. Nocistatin or nocistatin (10-17) produced no significant effect on basic pain threshold; however, both of them were found to reverse the effects of nociceptin in antagonizing endomorphin-1 and endomorphin-2 analgesia. CONCLUSION: Nocistatin and nocistatin (10-17) were shown to reverse the effects of nociceptin in antagonizing endomorphin-1 and endomorphin-2 analgesia at supraspinal level.