〔Abstract〕 Objective To investigate the neuroprotective effect of mesenchymal stem cells(MSC) combined with low-intensity transcranial ultrasound(LITUS) treatment on traumatic brain injury(TBI). Methods Seventy-two SD rats were randomly divided into four groups, namely, control group, TBI group, MSC injection group, and combined treatment group, with 18 rats in each group. TBI model was established by applying a pneumatic controlled cortical impingement instrument. Within 24 h after surgery, MSC was injected into the injury site by microinjector and microinjector pump using in situ injection. After injection, the injury site was treated with LITUS for 28 consecutive days using an ultrasound stimulator. The modified neurological functioning score(mNSS) was performed on rats in each group at 1, 3, 7, 14, 21 and 28 days postoperatively, and then the brains were extracted to detect pathological changes at the injury site and the mRNA and protein expression of brain-derived neurotrophic factor(BDNF), growth associated protein-43(GAP-43), postsynaptic density protein-95(PSD-95) and glial fibrillary acidic protein(GFAP) by HE staining, immunohistochemistry, Western blot and RT-PCR.Results Compared with the control group, the mNSS score increased in the TBI group(P<0. 05), the expression of GAP-43 and PSD-95 decreased, and the expression of GFAP increased(P<0. 05); Compared with the TBI group, the mNSS score of MSC group was lower(P<0. 05), the expression of BDNF, GAP-43, PSD-95 increased, and the expression of GFAP decreased(P<0. 05); mNSS scores were lower in the combined treatment group than those in the MSC group(P<0. 05), the expression of BDNF, GAP-43, PSD-95 increased, and the expression of GFAP decreased(P<0. 05).Conclusion The mechanism by which MSC combined with LITUS exerts neuroprotective effects in TBI may be related to the promotion of BDNF, GAP-43, and PSD-95 expression and reduction of GFAP expression.