BACKGROUND: Recently there have been several contradictory reports about the analgesic effects of opioids applied to peripheral tissues. To confirm the peripheral analgesic effects of opioids, this study compared the analgesic effects by observing the pain behavior in rats using the formalin test following infiltration of the commonly used opioids: morphine, meperidine and fentanyl. Furthermore, to confirm the mechanism of this analgesia, it also contrasted the differences of the analgesic effects between local infiltration and intraperitoneal injection of each opioid, and the reversal of peripheral analgesia of morphine by the administration of naloxone. METHODS: One hundred rats were divided into ten groups. The groups were a SHAM group(injection of normal saline 5 min before the formalin injection), infiltration groups(MSLO; 0.1 mL of 0.1% morphine 5 min before the formalin injection, DMLO for 1% meperidine, FTLO for 0.001% fentanyl), intraperitoneal groups(MSIP, DMIP, FTIP), reversal groups(MSLONAIP, MSLONALO) and a naloxone group(NALO). Under inhalation anesthesia, all animals were injected with an opioid according to their allocated group followed by the injection of 0.1 mL of 5% formalin in the plantar area of the hind paw. After recovery from anesthesia, all animals were observed for the number of flinches during phase 1(2~3 min, 5~6 min) and phase 2(every 1 min from 10 to 61 min) after the formalin injection. RESULTS: The flinches were significantly less in the infiltration groups(MSLO, DMLO, FTLO) than in the SHAM group(p<0.05). In addition, there were significantly different peripheral analgesia according to the type of opioid(p<0.05): morphine had a weak, prolonged but delayed onset of peripheral analgesia; meperidine had a potent, prolonged, rapid onset of analgesia but the number of flinches increased in the latter stages of the test; and fentanyl had a rapid, potent but very short duration of analgesia. Differences between peripheral and systemic analgesia were observed; the numbers of flinches in the DMLO, MSLO and FTLO groups were less than in the DMIP, MSIP and FTIP groups respectively(p<0.05). The reversals by naloxone applied locally or intraperitoneally did not increase the number of flinches in the groups of local infiltration of morphine. Furthermore, local infiltration of naloxone alone had less flinches than in the SHAM group(p<0.05). CONCLUSIONS: In this study, peripheral analgesia of opioids are readily present. Local infiltration of opioids such as morphine, meperidine and fentanyl has more potent analgesia than in systemic injection and the characteristics of these peripheral analgesia are different by the type of opioid. Moreover, these effects are not reversed by naloxone.