She left from her Gulshan residence around 10am.
Special Assistant to the BNP chief Shimul Biswas told bdnews24.com: "Madam will have her lunch at the Comilla Circuit House before joining the rally."
Meanwhile, the BNP has accused the government of trying to obstructing ahead of the rally.
"Local Awami League leaders and administration have ripped apart some of the welcome-arches at Comilla's Daudkandi and0 Chandina areas. They have also burnt banners meant for Saturday's rally," the rally committee convener and senior BNP leader Nazrul Islam Khan told bdnews24.com.
This would be Khaleda Zia's second public appearance in Comilla after 2008 and eighth since the Jan 5 general election.
On Nov 12, she addressed a rally in Kishoreganj following which she held a several meetings with different forums of the party over next programmes.
Though the BNP has been demanding for a poll under a 'non-party government', the ruling Awami League seems reluctant.
In a meeting on Friday, Prime Minister Sheikh Hasina made it clear that they have no plans to bring back the caretaker government system.