The clinical efficacy of microsurgical neck clipping for the treatment of cerebral aneurysm rupture and its effect on serum nuclear factor κ-light-chain-enhancer of activated β cells (NF-κB), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) levels were investigated. A total of 56 patients with first occurrence of cerebral aneurysm rupture were enrolled from June 2015 to June 2016. These patients were divided into control (25 patients) and observation groups (31 patients) according to treatment received. The patients in the control group were treated with interventional embolization and extraventricular drainage, while the patients in the observation group were treated with microsurgical neck clipping. Serum NF-κB, MCP-1 and MMP-9 levels were measured by ELISA prior to the operation and at 6 h post-operation. Clinical effects were compared at the 6-month follow-up. There was no significant difference in the success rate of the operation between the two groups (p>0.05). The incidence of complications in the observation group was significantly lower than that in the control group (p<0.05). The Glasgow Outcome Scale score was significantly improved in the observation group (p<0.05) compared with the control group. Serum NF-κB, MMP-9 and MCP-1 were significantly decreased in both groups at 6 and 24 h after operation, but the observational group showed significantly lower levels for all three proteins than the control group (p<0.05). The application of early microsurgical neck clipping for the treatment of cerebral aneurysm rupture can reduce complications and improve clinical prognosis, and this may be related to a decrease in serum inflammatory response-related factors (NF-κB and MCP-1) and MMP-9.