Mytilus coruscus adults were challenged by Vibrio splendidus in three concentrations (1×10⁶ cell/mL, 1×10⁷ cell/mL, 1×10⁸ cell/mL). The changes of immune indexes including nitric oxide synthase (NOS), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MAD), and digestive enzyme activities including amylase and protease in digestive gland were determined during 72 h experiment period. The activities of NOS in foot, gill and digestive gland were measured after experimental challenges of 48 h. Only the activity of NOS in the digestive gland was significantly different from the control group, and the activity of NOS increased with the increase of initial concentration of V. splebdidus. The activity of NOS of digestive gland in the treatment group was significantly higher than that of the control group after the challenge of V. splebdidu, and the level of NOS significantly increased after 48 h. The content of NO was significantly higher than that in the control group. The content of NO increased first and then decreased, which had a similar trend with the activity of NOS. The activity of SOD was significantly higher compared with that of the control group after the challenge of V. splebdidu. The content of MAD in the treatment group was significantly lower than that in the control group after the challenge of bacteria. The activity of amylase in the treatment group was significantly lower than that in the control group. The activity of amylase descended first and then increased. The change of protease activity in the treatment group increased first and then decreased. This study indicates that V. splebdidu can promote the immune indexes and protease activity and inhibit amylase activity. The present study provides useful information for clarifying the immune mechanism of M. coruscus and Vibrio-mussel interactions.