After Japan opened the ports to foreign trade, Osaka became the main portal of Kansai region and began its rapid industrialization. However, the international trade activities not only brought a high degree of economic development, but also caused serious plague epidemics. In the beginning of 20 century, the outbreak of plague lasted for about six years, from 1905 to 1910, spread over larger area, and resulted in 1,682 patients in both Hyogo and Osaka prefecture. It was by far the greatest plague epidemic in Japan that the administration conducted a large-scaled disease investigation and statistics. The reports about bubonic plague were so detailed that researchers can use these material to look inside the social and urban environment of Osaka during its rapid internationalization and industrialization. This study take advantage of GIS's visual power to analyze the prevalence of patients and its relationships with urban environments. GIS provides a new perspective to verify historical materials and transform the static value data into a dynamic and valuable time maps. The analysis shows the spread of plague in Osaka had closer relationship with commercial and transportation networks than with dweller's living status and their occupations. The prevail trail and the spatial aggregation were highly related to the canals and some specific areas near the river. One of the main targets of the executive authorities' anti-plague measures was the slums; however, there was a little victim found against our, and the executive authorities of those days' expectation. This study found that the plague pandemic in Osaka was not spread among the so-called dirty environment and among the specific social classes, but diffused in the inner city's canal networks, repeated a major blow to the particular area and population.