AIM: To determine whether Houttuynia cordata Thunb (HCT) can increase the survival of the retinal ganglion cells (RGCs) and inhibit microglia activation following retinal ischemia-reperfusion (RIR) injury. METHODS: Rat model of RIR was induced by transient elevation of the intraocular pressure (IOP). HCT was orally administered for 2d before the performance of retinal RIR model and once a day for the next 14d. After 14d of RIR injury, the rats were sacrificed for further analysis. Survival RGCs were stained with haematoxylin and eosin (H&E). Apoptosis of RGCs was detected by TUNEL staining. Retinal function was examined by flash-electroretinography (F-ERG). Retinal microglia were labeled using Iba-1, one specific marker for microglia. The mRNA expression levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) were assessed by quantitative real time reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Systemic HCT treatment significantly reduced RGCs death by H&E staining and exhibited an anti-apoptotic effect as assessed by TUNEL staining at day 14 after RIR injury. HCT greatly improved the retinal function as examined by F-ERG. The number of activated microglia significantly increased after RIR injury, which was significantly attenuated by HCT treatment. Besides, RIR injury induced a strong upregulation of pro-in?ammatory genes TNFα, iNOS and IL-1β mRNAs at day 14 post injury, which was suppressed by HCT. CONCLUSION: Neuroprotective effects of HCT encourage the survival of RGCs through inhibiting microglia activation due to RIR injury. Together these results support the use of HCT as promising therapy for the ischemic events of the retina diseases.