Background: Recent reports of the National Ministry of Health and Treatment of Iran (NMHT) show that Gilan has a higher annual incidence rate of leptospirosis than other provinces across the country. Despite several efforts of the government and NMHT to eradicate leptospirosis, it remains a public health problem in this province. Modelling and Prediction of this disease may play an important role in reduction of the prevalence. Methods: This study aims to model and predict the spatial distribution of leptospirosis utilizing Geographically Weighted Regression (GWR), Generalized Linear Model (GLM), Support Vector Machine (SVM) and Artificial Neural Network (ANN) as capable approaches. Five environmental parameters of precipitation, temperature, humidity, elevation and vegetation are used for modelling and predicting of the disease. Data of 2009 and 2010 are used for training, and 2011 for testing and evaluating the models. Results: Results indicate that utilized approaches in this study can model and predict leptospirosis with high significance level. To evaluate the efficiency of the approaches, MSE (GWR = 0.050, SVM = 0.137, GLM = 0.118 and ANN = 0.137), MAE (0.012, 0.063, 0.052 and 0.063), MRE (0.011, 0.018, 0.017 and 0.018) and R 2 (0.85, 0.80, 0.78 and 0.75) are used. Conclusion: Results indicate the practical usefulness of approaches for spatial modelling and predicting leptospirosis. The efficiency of models is as follow: GWR > SVM > GLM > ANN. In addition, temperature and humidity are investigated as the most influential parameters. Moreover, the suitable habitat of leptospirosis is mostly within the central rural districts of the province.