Intracerebral hemorrhage (ICH) is a lifethreat-ening type of stroke. Previous studies have reported that bone marrow mesenchymal stem cells (BMSCs) may exert beneficial effects on the treatment of ICH. However, it remains unknown whether the neuroprotection exerted by BMSCs on ICH is due to the differentiation of BMSCs, or the trophic factors secreted into their conditioned medium (CM). In addition, growth-associated protein-43 (GAP-43) is a protein associated with neurite extension, which may be considered a prospective therapeutic target in the treatment of ICH. The present study investigated whether administration of BMSC-CM could be considered as an alternative to the established treatment of direct BMSC transplantation; in addition, the underlying mechanisms were evaluated. Neurological function tests, brain water content, reverse transcription -quantitative polymerase chain reaction and western blotting were used in present study. The current study indicated that the neuroprotective effects of BMSC implantation and BMSC-CM treatment are similar, and that both decrease the severity of post-ICH cerebral edema, as well as improving neurological functions. At the molecular level, treatment with BMSC-CM resulted in a marked elevation in the expression of GAP-43 and interleukin (IL) -10, in addition to a significant reduction in the expression levels of IL-1a, tumor necrosis factor-a and IL-6. Following application of a phosphorylated-extracellular signal-regulated kinase (ERK1/2) inhibitor, PD98059, in a BMSC-CM rat model, the mRNA and protein expression levels of GAP-43 were significantly attenuated. Therefore, the findings of the present study demonstrated that treatment with BMSC-CM may be an alternative to direct BMSC transplantation in a rat model of ICH. The mechanism underlying BMSC-CM-mediated neuroprotection may be associated with anti-inflammatory effects, as well as activation of GAP-43 transcription and expression through ERK-1/2 phosphorylation. Therefore, the ERK-1/2-GAP-43 signaling pathway may be considered a potential novel application target of BMSC-CM for the treatment of neurological diseases.