Difference in meaning, no, but difference in use, yes. Sometimes, you can use eirher; example: "Lots of people turned up to today's protest". "A lot of people turned up to today's protest". Sometimes, however, one would be incorrect; example: "A lot of the time, I feel as though life is pointless." - correct "Lots of the time, I feel as though life is pointless." - incorrect.

http://www.differencebetween.net/language/words-language/difference-between-a-lot-of-and-lots-of/