Background: Chronic pain and related complications reported after the use of perforating fixation devices in hernia surgery have led to the use of tissue sealants. Fibrin sealant is a feasible option for mesh fixation; however data on cyanoacrylate glues are limited. Methods: 32 Sprague-Dawley rats were divided into two groups and a 1.5 cm abdominal wall defect was created on each animal. The lesions were then repaired with 2 x 2 cm polypropylene meshes, fixed with n-butyl-cyanoacrylate in the first group and with polypropylene sutures in the second group. The rats were sacrificed on the 21st and 42nd days. The presence of infection, recurrence, and abdominal adhesions were evaluated, followed by biomechanical testing and histological examination. Results: No mesh infection or hernia recurrences were recorded. There was no statistically significant difference between neither the adhesion scores nor the mean broken pressure of the two groups. Cyanoacrylate sealing was found equivalent to suturing in terms of tissue ingrowth, fibrosis, inflammatory infiltration, abscess formation, and necrosis. Furthermore, cyanoacrylate resulted in less foreign body reaction. Conclusions: Mesh fixation by cyanoacrylate may be considered as an alternative to suture fixation.