I2C is a serial protocol for two-wire interface to connect low-speed devices like microcontrollers, EEPROMs, A/D and D/A converters, I/O interfaces, and other similar peripherals devices. The original I2C bus had a maximum speed of 100 KHz and most common applications still use this speed. Later the maximum speed was increased to 400 kHz in fast mode. The ETS platform provides an up to 466KHz speed fast mode I2C bus for application expansion. An I2C bus has two signals, along with a power and shared ground connection, one primary and multiple secondaries. The I2C bus is quite stable when the two signals’ connections are short and there are only several secondary devices but it changes dramatically when the physical connections are longer, the number of secondary devices increases, and the communication speed is high. This situation is becoming more and more common as the complexity of application hardware increases. This presentation will discuss the principle of I2C bus communication and how to deal with longer cable connections, many secondary devices and the isolation application of I2C bus.