BACKGROUND: Zoonotic cutaneous leishmaniasis (ZCL) is a neglected tropical disease worldwide, especially the Middle East. Although previous works attempt to model the ZCL spread using various environmental factors, the interactions between vectors (Phlebotomus papatasi), reservoir hosts, humans, and the environment can affect its spread. Considering all of these aspects is not a trivial task. METHODS: An agent-based model (ABM) is a relatively new approach that provides a framework for analyzing the heterogeneity of the interactions, along with biological and environmental factors in such complex systems. The objective of this research is to design and develop an ABM that uses Geospatial Information System (GIS) capabilities, biological behaviors of vectors and reservoir hosts, and an improved Susceptible-Exposed-Infected-Recovered (SEIR) epidemic model to explore the spread of ZCL. Various scenarios were implemented to analyze the future ZCL spreads in different parts of Maraveh Tappeh County, in the northeast region of Golestan Province in northeastern Iran, with alternative socio-ecological conditions. RESULTS: The results confirmed that the spread of the disease arises principally in the desert, low altitude areas, and riverside population centers. The outcomes also showed that the restricting movement of humans reduces the severity of the transmission. Moreover, the spread of ZCL has a particular temporal pattern, since the most prevalent cases occurred in the fall. The evaluation test also showed the similarity between the results and the reported spatiotemporal trends. CONCLUSIONS: This study demonstrates the capability and efficiency of ABM to model and predict the spread of ZCL. The results of the presented approach can be considered as a guide for public health management and controlling the vector population .