Aim: To investigate the efficacy of tissue adhesives for closing the orifice of the inguinal hernia sac (HIS) as an alternative method for treating inguinal hernia. Methods: Five-week-old male Lewis rats (n = 54) were used, because Lewis rats have a large patent HIS. The rats were divided into 9 groups (n = 6 in each) according to the type of tissue adhesive used: G1, fibrin glue (Beriplast (R)); G1b, Beriplast (R) plus blood; G2, microfibrillar collagen hemostat (Avitene (R)); G2b, Avitene (R) plus blood; G3, fibrinogen-based sealant (TachoComb (R)); G3b, TachoComb (R) plus blood; G4, synthetic absorbable sealant (Advaseal (R)); G5, bilateral single port laparoscopic injection of octylcyanoacrylate (Dermabond (R)); and G6, sham operation (control group). In G1-G4, surgery was performed through a midline lower abdominal incision. In G5, a 5-mm laparoscope was inserted in the epigastrium, a fine catheter was passed through the side port of the laparoscope into the right HIS, and 0.2 mL Dermabond was injected. The left HIS was treated in the same way. All rats were sacrificed 3 months after treatment, and HIS patency was examined macroscopically. All rats in G5 and G6 were mated 50 days after treatment to check fertility. Results: All rats survived until sacrifice. At sacrifice, all IHS were patent in G6. All HIS were also patent in G1-G4, but all HIS were closed at the internal ring in G5. In G5 there were no adhesions between the orifice of the closed sac and the small bowel in 5/6, and only minor adhesions in 1/6. G5 fertility (5/6: 83%) was the same as for the control group (G6). Conclusion: Our results suggest that laparoscopic injection of Db into the HIS is simple, safe, reliable, virtually scarless, and may be a reasonable alternative to standard open surgical inguinal hernia repair.