In order to explore the effects of salinity stress on the immunity of the Nile tilapia (Oreochromis niloticus), we conducted acute and chronic salinity stress experiments on tilapia with body weight of (35±5) g and some immune-related parameters of the serum were tested. In acute salinity stress, the salinities of 0, 5 and 15 were set, and the enzyme activities of SOD, CAT, GSH-Px and AKP in serum were detected by sampling at 6, 12, 24, 48 and 96 h after stress respectively. In the chronic experiment, four salinity levels of 0, 10, 20 and 30 were set, and the enzyme activity of SOD, CAT, GSH-Px and AKP in serum was detected after 8 weeks of stress. The results showed that: SOD activity in serum increased with salinity at 6, 12 and 24 h under acute salinity stress, but at 96 h, enzyme activity in the salinity 15 group was significantly lower than that in 5 group. Under chronic salinity stress, the enzyme activity of each group decreased significantly with the increase of salinity. CAT activity in serum decreased significantly with the increase of salinity at 12 h and 24 h under acute salinity stress, and there was no significant difference after that. GSH-Px activity in serum decreased significantly with the increase of salinity at 6, 12 and 48 h after stress. AKP activity in serum significantly decreased with the increase of salinity at 6h after stress. Under chronic stress, the 20 group was significantly lower than the other groups. In the experiment of susceptibility to Streptococcus agalatiae after chronic stress, the susceptibility of the salinity 10 group to S. agalatiae had no obvious difference compared with 0, the susceptibility of 20 and 30 groups were higher than 0 group. This study showed that both kinds of stress could cause changes in immune-related indicators: acute salinity stress experiment showed that the salinities of 5 and 15 caused oxidative damage to the tilapia, but tilapia could gradually adapt to this change. Chronic salinity stress experiment showed that salinity above 20 could inhibit the activity of many immune indicators of tilapia, resulting in increased susceptibility to S. agalatiae.