Objective To explore the protective effect of hydrogen (H₂) inhalation through respiratory tract on monoarthritis (MA) rats. Methods Forty male SD rats were randomly divided into 5 groups:MA group, MA+H₂ 0-14 d group, MA+H₂ 0-3 d group, MA+H₂ 4-14 d group, and sham+H₂ 0-14 d group (n=8). Complete Freund's adjuvant (CFA) was injected into the left ankle joint of rats to construct MA model. The rats in the MA group did not inhale H₂, and the rats in other four groups inhaled 65% H₂ 1.5 h per day on the day of modeling and 1-14 days after modeling, 1.5 h per day on the day of modeling and 1-3 days after modeling, 1.5 h per day on the 4^th-14^th day after modeling, and 1.5 h per day on the day of sham operation and 1-14 days after modeling, respectively. Paw withdrawal threshold (PWT) was detected by von Frey method 0, 1, 3, 5, 7, 10, and 14 d after modeling. Another 15 rats were randomly divided into 5 groups and there were 3 rats in each group. Lumbar enlargement tissues were taken from the spinal cord of the inflammatory side on the 10th day after modeling or sham operation. The contents of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were detected. Results In the MA group, the posterior paw PWT of the inflammatory side was lower than that of the healthy side on the first day after modeling, reached the lowest on the 3th day and remained stable until the 14^th day (P<0.01). The PWT of the inflammatory side of the hind claw of rats in the MA+H₂ 0-14 d group and the MA+H₂ 0-3 d group was higher than that in the MA group (P<0.05, P<0.01). The PWT of the inflammatory side in the MA+H₂ 4-14 d group was not significantly different from that in the MA group (P>0.05). The levels of SOD and CAT in the spinal cord of the inflammatory side in the MA+H₂ 0-14 d group were higher than those in the MA group (all P<0.05), while MDA level was lower than that in the MA group (P<0.05). Compared with MA group, there was no significant difference in the SOD, CAT or MDA level in the MA+H₂ 0-3 d group and MA+H₂ 4-14 d group (all P>0.05). Conclusion Inhalation of 65% H₂ via the respiratory tract at the initial stage of MA rat modeling can alleviate mechanical hyperalgesia and oxidative stress. Pre-administration of H₂ can inhibit the formation of mechanical hyperalgesia in MA.