This study aimed to compare three most widely used surgeries for experimental lumbar spinal drug delivery in rats. The comparison consisted of assessing the effects of the surgeries and evaluating the deficits produced by these three methods. Sprague Dawley rats underwent acute needle puncture, chronic catheterization via laminectomy or nonlaminectomized catheterization. Body weight changes were measured, animals' general and neurological conditions were observed after surgeries, and motor function was examined by Rota Rod test both prior to and post surgery. Furthermore, nociceptive tests were performed to assess the animals' nociception; hematoxylin, and eosin staining of lumbar spinal cord tissue was performed to evaluate local inflammation caused by surgeries; and both lidocaine paralysis detection; and toluidine blue dye assay were used to confirm the exact location of the catheter. Both needle puncture and catheterization via laminectomy had relatively low success rate of surgery and induced various neurological signs; more severe motor dysfunction, hyperalgesia, allodynia, and local inflammation. Nonlaminectomized catheterization had a higher success rate of surgery, and induced only mild agitation, slight cerebral spinal fluid leakage, mild sensory and motor abnormalities, and minimum pathology in the lumbar spinal cord. The nonlaminectomized catheterization used in this study induces a phenotype of less detectable effects on the animal's behavior and is well-tolerated compared to the acute needle puncture and laminectomized catheterization that are widely used in the literature. Nonlaminectomized catheterization is a safe, accurate and effective way for lumbar drug delivery in rats. Anat Rec, 2012. (C)2012 Wiley Periodicals, Inc.