Objective To study the effect of acupuncture on the TLR2/4-NF-?B signalling pathway in the cortex of Sprague-Dawley rats following traumatic brain injury (TBI), and investigate the possible mechanism underlying the effects of acupuncture on scar repair.Methods TBI was established using Feeney's free-falling epidural percussion model. In total, 108 rats were randomly divided into a normal group (n=18), untreated TBI model group (TBI group, n=36) and manual acupuncture-treated TBI group (TBI+MA, n=36). Each group of rats was subdivided into three time groups: 3-day (3d), 7-day (7d) and 14-day (14d). No treatment was given to rats in the normal and TBI groups. The TBI+MA?group received manual acupuncture at GV20, GV26, GV16 through GV15, and bilateral LI4. mRNA expression of TLR2, TLR4, NF-?B and protein in the rat cortices was quantified using real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blot analyses.Results The modified neurological severity score (mNSS) scores of the TBI+MA?group were improved compared with baseline scores 12?hours after modelling, and improved at 7d and 14d compared with the TBI group (P<0.05), while the score of the TBI group did not improve until 14d compared to baseline. mRNA and protein expression of TLR2, TLR4 and NF-?B in the TBI group were higher than the normal group at 3d (P<0.05), reached a peak at 7d, then began to decrease at 14d. mRNA and protein expression of TLR2, TLR4 and NF-?B were higher in the TBI+MA?group compared with the TBI group at 3d (P<0.05), were significantly down-regulated at 7d (P<0.01), and decreased to normal levels at 14d.Conclusions Acupuncture has a bidirectional regulatory effect on the TLR2/4-NF-?B signalling pathway-related genes TLR2, TLR4 and NF-?B in the TBI rat cortex, promoting their expression in the early stage and inhibiting it in the later stage.