In this article, we describe a simple and facile approach for the production of I-125 from the neutron-irradiated natural Xe using wet chemical distillation. First, we outline the design of the irradiation container, its fabrication, cryogenic loading of the gaseous Xe target into the irradiation container, and hermetic sealing of the irradiation container. Quality-assurance tests of the irradiation containers were performed to ensure their safety during neutron irradiation. In light of the implicit need to obtain I-125 activity with minimum I-126 radionuclidic contamination, the irradiation time, neutron flux, and target cooling time were judiciously optimized. A thorough optimization of experimental parameters of distillation was carried out to obtain the optimal yield of I-125 having the desired purity. In each batch, typically 4 g of natural xenon gas was irradiated in the BARC Dhruva reactor for 15 days with a thermal neutron flux of approximately 5 X 10(13) cm(-2) s(-1). After irradiation, the targets were left to decay for typically similar to 50 days to reduce the I-126 contamination. Several batches of I-125 were successfully produced using the developed procedure at a level of similar to 18.5 GBq (500 mCi) I-125 per batch. The I-125 quality in terms of radionuclidic purity, radiochemical purity, and radioactive concentration was evaluated and found to be acceptable for radiolabeling studies. This reported method currently has been adapted for the routine production of I-125 to meet local needs.