Spinal cord injury (SCI) is a devastating disease leading to motor disability. Metabolic dysfunction is another complication of SCI. Thus, we aimed to study the effect of SCI on the histological and biochemical structure of the liver in adult male rats and to delineate the role of post-injury administration of G-CSF. Thirty adult male Sprague-Dawley rats were assigned into three groups: Group I; control (18 rats subdivided equally into three subgroups), and 12 rats underwent SCI and were divided into an SCI group II and G-SCF-treated group III. Twenty-one days post-injury, liver sections were processed for light and electron microscopic examinations and immunohistochemical staining for PCNA and CD68 antibodies. The biochemical assay was carried out for detection of serum levels of ALT, AST, total proteins, albumin, total cholesterol, triglycerides, HDL-c, GSH and MDA. Liver tissue levels of GPx and MDA as well as semiquantitative RT-PCR analysis of hepatic cytokine expression were also conducted. In the SCI group, results showed liver tissue damage in the form of lipid infiltration, blood vessel congestion, vacuolated cells with apoptotic nuclei and increased collagen deposition. Increased CD68-positive macrophages and a decreased number of PCNA-positive cells was detected. Moreover, liver enzymes, total cholesterol and triglycerides were increased while serum albumin, total proteins and HDL-c were decreased in the SCI group. Oxidative stress and increased expression of inflammatory cytokines were detected. Administration of G-CSF induced significant liver improvement with retained liver function by antiinflammatory, immune-modulatory and antioxidant mechanisms.