The impacts of zinc oxide nano-extract from O. majorana leaves on the histological structure of the lung of albino rats were investigated in the current study. There were fourty- two rats that are rats are divided into six groups of seven animals. The first group (negative control) received 0.3 ml of normal saline subcutaneously. The second group (positive control group) received L. donovani parasite injections. The third group treatment with nano extract of zinc oxide (10 mg/kg) from O. majorana leaves was given subcutaneously. The fourth treat with nano extract of zinc oxide (15 mg/kg) from O. majorana leaves, fifth, and sixth groups got nano-extractors (10 and 15 mg/kg) and were infected with L.donovani. The animal was subsequently given 0.3 ml of nano-extract three times a week for a month. Moreover, the findings revealed that there are several changes in their lung structure; inflammatory cell infiltration into the alveolar gaps, eosinophilic inflammation, regenerative proliferation of airway epithelial cells, and thickening of the bronchial muscle wall were frequently seen. After exposure to low levels of ZnO NPs., lymphocytes and eosinophils grew somewhat. Mild increases in lymphocytes and eosinophils were seen after exposure to low doses of ZnO NPs in L.donovani-infected tissue. The histological changes on the lung treated with Nano-extract (zinc oxide) of the O. majorana leaves at different concentrations were employed for treating the histological shifts and reducing the damage caused by the parasite. Thus, the effectiveness of the nano-extract is effective in reducing the influences and resisting the parasite. Histological changes in the lung in groups treated with the nano extract showed resistance to the parasite in terms of its lack of effect on causing histological changes compared to the positive control group. The concentration of the crude essential oil, which was (15mg/ml), gave the highest percentage of growth inhibition for the parasite lung tissue and showed few fibrosis around the alveolar sacs in the group treated. In contrast, the second concentration of the essential oil, which was (10mg/ml), showed a lower percentage of inhibition and cellular killing of the parasite’s visceral cells. Aim of study: There is a need for novel therapeutic techniques. Recent breakthroughs in nanosystems have investigated passive and active targeting ways to increase medication concentrations while reducing undesirable toxicity and side effects to healthy tissues. The utilization of nanoparticles for targeted drug delivery has the potential to reduce medication dosage and address difficulties linked to conventional drug treatment, including rapid clearance, insolubility in aqueous environments, and a lack of selectivity that leads to non-specific cellular toxicity.