Xanthomonas oryzae pv. oryzae (Xoo) is an important rice pathogen.  This is a vascular pathogen entering the plant via the hydathodes causing rice bacterial blight.  It has been known that most regulation of pathogenicity factor F (RpfF) genes in Xanthomonas regulates virulence in response to the diffusible signal factor (DSF).  The RpfF recognized as an attractive drug target in bacterial rice blight disease.  In this study, we performed the gene-gene interaction of RpfF and pathway functional analysis.  3D structure of RpfF protein was predicted using a homology modelling tool Swiss-Model and refined by molecular dynamics (MD) simulation.  The refined model protein was predicted structural assessment using various tools such as PROCHECK, ERRAT, and VERIFY-3D.  We have collected 2 500 rifampicin analogues from Zinc Database by virtual screening.  The screened compounds were docked into the active site of the RpfF protein using AutoDock Vina in PyRx Virtual Screening Tool.  Furthermore, docking result and in silico ADMET analysis described that the compounds ZINC03056414, ZINC03205310, ZINC08673779, ZINC09100848, ZINC09729566, ZINC11415953, ZINC12810788, ZINC24989313, ZINC27441787 and ZINC32739565 have best binding energies and less toxicity than reference compound.  This study revealed that the active site residues such as HIS-118, HIS-147, THR-148, ARG-179, ASP-207, ARG-240 and THR-244 are key roles in the pathogenicity.  It could be beneficial in the design of small molecule therapeutics or the treatment of rice bacterial blight disease.