The aim of this study was to investigate whether enoxaparin (ENX) administration would increase seroma risk and worsen mesh tissue recovery in an experimental rat hernia repair model. Fifty-six adult male Wistar–Albino rats were included in the study. Rats were equally and randomly separated into seven groups: Group 1, Control, only subcutaneous dissection was performed; group 2, Sham, Hernia defect was primary sutured; Group 3, Prolene mesh; Group 4, Dual mesh; Group 5, ENX + Sham; Group 6, ENX + Prolene mesh; Group 7, ENX + Dual mesh. ENX was subcutaneously injected at a dose of 180 U/kg per day for 7 days. Rats were killed after the amount of subcutaneous seroma was determined by ultrasound on day 7 following the surgical procedure. Mesh-tissue healing was evaluated using histopathological and immunohistochemical (CD31) staining methods. The mean seroma amount significantly increased in Groups 5–7 compared to Groups 2–4. CD31 immunostaining showed a reduction in neovascularization in Groups 6 and 7, compared to Groups 3 and 4. Neovascularization decreased and hemorrhage, necrosis and oedema findings remarkably increased in Groups 6 and 7, when compared to Groups 3 and 4. Fibroblastic activity and inflammation were more prominent in Groups 3 and 4. It should be kept in mind that ENX interferes with inflammation, which is desired in the early period of healing and leads to an increase in overall seroma amount with anti-coagulant effects, which in turn may disrupt wound healing and mesh-tissue adhesions, as was indicated in our study.