In 2000, development began on a prototype platform for supporting multilevel modeling, under the leadership of Professor Taishin Nomura at the BioDynamics Laboratory of Osaka University. The platform was named insilicoIDE (ISIDE) in 2006, and at the same time, insilicoML (ISML) was developed as the model description language. In 2007, development began on the insilicoSim simulator and insilicoDB database with the aid of the MEXT Global Center of Excellence program for “an In Silico Medicine-Oriented Worldwide Open Platform” at Osaka University (Leader: Prof. Taishin Nomura, Osaka University, 2007–2011).
In 2010, the PhysioDesigner project was started by Dr. Hiroaki Kitano in collaboration with Prof. Taishin Nomura, SBI, and all developers of ISIDE. PhysioDesigner officially took over the development stream from ISIDE in 2011, and its development was carried on in Okinawa Institute of Science and Technology (OIST). All functions implemented on ISIDE were reimplemented on PhysioDesigner and new features were added. PHML was also developed concurrently with PhysioDesigner, inheriting ISML specifications. Concurrently insilicoSim was succeeded by Flint, which is now opened at GitHub.
In 2016, the chief developer since 2007, Dr. Yoshiyuki Asai, has moved to Yamaguchi University as a professor. Yamaguchi became a main site to develop and maintain PhysioDesigner with collaboration with Osaka university, OIST and the Systems Biology Institute (SBI).