Abstract: Background and Objective: Artequin (ATQ) is an artemisinin combination therapy antimalarial drug, effective against all stages of Plasmodium falciparum. The aim of this study was to investigate its effects on the hippocampal microstructure and immunoreactivity, as well as the neurobehaviour of adult Wistar rats. Materials and Methods: Forty-two inbred adult male Wistar rats of average weight 200 g were divided into groups 1-6 (n = 7) of control (5 mL kg–1 of distilled water) and test groups receiving oral doses of 0.86/1.07 mg kg–1 (ATQ1), 1.71/2.14 mg kg–1 (ATQ2), 3.42/4.28 mg kg–1 (ATQ3), 6.84/8.56 mg kg–1 (ATQ4) and 13.68/17.12 mg kg–1 (ATQ5) body weight of ATQ for 3 days. Morris water neurobehavioural test was carried out for 2 days each, prior and after the administrations. The animals were sacrificed after ketamine hydrochloride anaesthesia and perfusion-fixed using 10% buffered formalin. They were routinely processed using haematoxylin and eosin and silver impregnation methods. Representative sections were immunolabeled for glial fibrillary acidic protein (GFAP). Results: Except for ATQ1 group, other ATQ groups had significantly (p<0.05) higher escape latency compared with the control. The hippocampus of the ATQ groups showed histopathological features including hypertrophy, pyknosis, karyorrhexis and less (p<0.05) cell population, with increased expressions of glial fibrillary acidic protein compared with the control. Conclusion: ATQ administration induced dose-dependent adverse effects on the hippocampal microstructure and GFAP immunolabeling, as well as on learning behaviour. This may suggests neuronal and glial pathology which may lead to neuronal and glial degeneration, ultimately resulting in altered functional processes of this brain area.