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Background: Diabetic peripheral neuropathy (DPN) is the most common cause of neuropathy worldwide, with oxidative and inflammatory being the pathways involved. Red fruit (Pandanus conoides Lamk) is a plant native to Papua, Indonesia. Red fruit oil (RFO) is known to have potent antioxidant and antiinflammatory activities. Aims and Objective: To evaluate the effects of RFO in a rat model of streptozotocin-induced diabetic neuropathy. Methods: Male Wistar rats were induced with 55 mg/kg streptozotocin intraperioteally. Rats with fasting blood glucose >200 mg/dL were assigned into groups treated with vehicle, pregabalin, and 0.3, 0.6, or 1.2 mL/kg RFO, respectively. Treatments were given for 3 weeks after a 6-week induction period was completed. Neuropathic pain was evaluated by thermal hyperalgesia testing. Histopathological changes of sciatic the nerve were evaluated by the Gaussian adaptive threshold method. Feed and drinking intake, blood glucose levels, body weight, and the sciatic nerve proinflammatory cytokines were also measured. Results: There were increases in blood glucose levels, feed and drink intake, MDA, TNF-alfa, IL-6, iNOS, NFkB and the number of damaged nerve cells in the DPN rat model when compared with normal rats (p<0.05). Decreased weight, number of pancreatic B cells, latency time of thermal hyperalgesia were also observed in DPN rats. A decrease in NRF2 and HO was observed in DPN rats but was not different compared with the normal group. RFO improved blood glucose, feed and drink intake, body weight, MDA and IL-6 levels, B-cell counts, the sciatic nerve presentation, and thermal hyperalgesia, although they did not return to normal value. Pregabalin did not affect blood glucose levels, body weight or pancreatic B cells but improved thermal hyperalgesia, the nerve cell counts, TNF-alfa, iNOS, IL-6, dan NFkB. Discussion and Conclusion: Overall, results of the present work indicate that RFO recovers DPN through the involvement of the oxidative and neuroiflammatory pathways. [ABSTRACT FROM AUTHOR]