The easiest way to get into Inle Lake (and the most comfortable) is by domestic flight. The closest airport is in Heho, which is a taxi-ride (about 1 hour) away from the lake itself (walking down the road from the airport, towards the highway, should see quoted fares drop, if not, try your luck hailing a taxi or passing pickup on the highway itself). Taking a taxi from the airport can be quite expensive, from 25 000 - 40 000 Kyats. By comparison a taxi from Yangon airport to the city centre (45 min.) is just 6000 Kyats or 7 USD. A good way to save money is to book a taxi in advance with your guesthouse, they usually charge about 15 000 Kyats. Prices for flights are around US$75 from Yangon and US$40 from Mandalay, but unlike bus companies the government is heavily involved in the domestic air market, a good chunk of your money will be going into their hands.
A cheaper, but less comfortable, option is that which most Myanmar people take - the bus. Buses depart daily, and cost around US$20 from Yangon (13 hours) or time from Mandalay. A very slow and uncomfortable bus is available for $9 from Bagan. These buses will get you there, but they are not really designed for larger westerners, and are quite cramped (passengers picked up along the way often end up sitting in the aisle). Overnight buses do run and with the new road between Yangon and Nay Pyi Taw the time taken for the trip has been shortened. Large Westerners can squeeze in OK and if they have booked ahead will have a seat; wealthy locals will book two seats to ensure greater comfort. Do not expect much sleep on over night trips as loud music and or video will be played over a screen at the front of the bus.